OBJECTIVE: To study the expression and function of L-type amino acid transporter 1 (LAT1), a major catalytic subunit of system L that is responsible for the transport of large neutral amino acids, including most essential amino acids, in concert with the covalently bound 4F2 heavy chain, and is implicated in tumorigenesis. METHODS: Human glioma cell lines and tumor specimens were analyzed for LAT1 expression using Western blotting and reverse transcription polymerase chain reaction analysis. The rate of neutral amino acid uptake was measured using L-[C]leucine. The proliferation and apoptosis rates were analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and terminal deoxynucleotidyl transferase-mediated nick end-labeling assays, respectively, on inhibition of system L by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. The effects on proliferation and tumor growth caused by exogenously overexpressed LAT1 were similarly analyzed. RESULTS: LAT1 was expressed in most human high-grade gliomas and glioma cell lines at various levels, with more ubiquitous expression of 4F2 heavy chain. Glioma cells with high LAT1 expression exhibited a marked increase in the uptake rate of L-[C]leucine. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid treatment not only suppressed deoxyribonucleic acid synthesis in association with the up-regulation of the cyclin-dependent kinase inhibitor p21 but also enhanced apoptosis with caspase activation, thereby exerting both cytostatic and cytocidal effects in glioma cells with high LAT1 expression levels. Furthermore, overexpression of LAT1 in glioma cells with low endogenous LAT1 expression significantly enhanced the rates of tumor cell growth in athymic mice. CONCLUSION: LAT1, the major transporter of system L, is frequently expressed at higher levels in high-grade gliomas than in low-grade gliomas and brain tissues, and it may play an important role in enhancing the rates of tumor cell proliferation and growth in vivo.
OBJECTIVE: To study the expression and function of L-type amino acid transporter 1 (LAT1), a major catalytic subunit of system L that is responsible for the transport of large neutral amino acids, including most essential amino acids, in concert with the covalently bound 4F2 heavy chain, and is implicated in tumorigenesis. METHODS:Humanglioma cell lines and tumor specimens were analyzed for LAT1 expression using Western blotting and reverse transcription polymerase chain reaction analysis. The rate of neutral amino acid uptake was measured using L-[C]leucine. The proliferation and apoptosis rates were analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and terminal deoxynucleotidyl transferase-mediated nick end-labeling assays, respectively, on inhibition of system L by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. The effects on proliferation and tumor growth caused by exogenously overexpressed LAT1 were similarly analyzed. RESULTS:LAT1 was expressed in most human high-grade gliomas and glioma cell lines at various levels, with more ubiquitous expression of 4F2 heavy chain. Glioma cells with high LAT1 expression exhibited a marked increase in the uptake rate of L-[C]leucine. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid treatment not only suppressed deoxyribonucleic acid synthesis in association with the up-regulation of the cyclin-dependent kinase inhibitor p21 but also enhanced apoptosis with caspase activation, thereby exerting both cytostatic and cytocidal effects in glioma cells with high LAT1 expression levels. Furthermore, overexpression of LAT1 in glioma cells with low endogenous LAT1 expression significantly enhanced the rates of tumor cell growth in athymic mice. CONCLUSION:LAT1, the major transporter of system L, is frequently expressed at higher levels in high-grade gliomas than in low-grade gliomas and brain tissues, and it may play an important role in enhancing the rates of tumor cell proliferation and growth in vivo.
Authors: Evan Augustyn; Karissa Finke; Arik A Zur; Logan Hansen; Nathan Heeren; Huan-Chieh Chien; Lawrence Lin; Kathleen M Giacomini; Claire Colas; Avner Schlessinger; Allen A Thomas Journal: Bioorg Med Chem Lett Date: 2016-04-11 Impact factor: 2.823
Authors: Olivia Kertels; Almuth F Kessler; Milena I Mihovilovic; Antje Stolzenburg; Thomas Linsenmann; Samuel Samnick; Stephanie Brändlein; Camelia Maria Monoranu; Ralf-Ingo Ernestus; Andreas K Buck; Mario Löhr; Constantin Lapa Journal: Mol Imaging Biol Date: 2019-12 Impact factor: 3.488
Authors: Aida Rashidi; Jason Miska; Catalina Lee-Chang; Deepak Kanojia; Wojciech K Panek; Aurora Lopez-Rosas; Peng Zhang; Yu Han; Ting Xiao; Katarzyna C Pituch; Julius W Kim; Mahsa Talebian; Jawad Fares; Maciej S Lesniak Journal: Cancer Immunol Immunother Date: 2019-12-16 Impact factor: 6.968
Authors: David O Kamson; Sandeep Mittal; Natasha L Robinette; Otto Muzik; William J Kupsky; Geoffrey R Barger; Csaba Juhász Journal: Neuro Oncol Date: 2014-03-26 Impact factor: 12.300
Authors: Csaba Juhász; Diane C Chugani; Geoffrey R Barger; William J Kupsky; Pulak K Chakraborty; Otto Muzik; Sandeep Mittal Journal: Clin Nucl Med Date: 2012-09 Impact factor: 7.794